Friedel-Crafts reactions (acylation and alkylation) are among the basic reactions used to synthesize functionalized aromatic compounds, which are extremely important intermediates for pharmaceutical products and fine chemicals. Prior-art liquid and solid Lewis and Brønsted acids are used as catalysts for Friedel-Crafts reactions.
The acidity of the catalyst affects the reaction kinetics of Friedel-Crafts reactions in many ways. For instance, the stronger the acidity of the catalysts, more easily deactivated aromatic compound can be used. The higher acidity also results in an improved reaction selectivity, for example in Fries rearrangement reactions. The usual acids in the chemical industry today are sulfuric acid and AlCl3, In various modifications.
An acidic reactant also known is an acidic ionic liquid, which is a salt having a melting point of less than 100° C., can be used in Friedel-Crafts reactions as well. The systems employed to date are those formed by adding a molar excess of a Lewis acid to the halide salt of an imidazolium, pyridinium, ammonium, or phosphonium ion. One example is a mixture of Imidazolium chloride salt with a molar excess of AlCl3. These acidic chloroaluminate molten substances are used to catalyze organic reactions in place of solid AlCl3, so that the disadvantage of the low solubility of AlCl3 in most organic solvents Is minimized. Examples in the literature include the reaction of benzene and toluene with various alkyl chlorides in a mixture of 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) and AlCl3 (4 parts [EMIM]Cl/6 parts AlCl3); and the alkylation of benzene with ethylene to form ethylbenzene using a liquid catalyst phase that is a mixture of an imidazolium chloride salt having a molar excess of AlCl3 or a molar excess of GaCl3.
An early example of a Friedel-Crafts acylation in an ionic liquid used a mixture of an imidazolium chloride salt with a molar excess of AlCl3 as a catalytically active phase, also describing that the rate of reaction increased with the increase of the percentage of the Lewis acid AlCl3 in the mixture.
The synthesis of some industrially important fragrance compounds (for example: Traseolid®) by means of Friedel-Crafts acylation in an acidic mixture of [EMIM]Cl-AlCl3(X(AlCl3)=0.67) has also been described. Again, an acceleration of the reaction was observed when the percentage of AlCl3 was increased further in the mixture. However, in the [EMIM]Cl-AlCl3, the molar percentage of AlCl3 cannot be increased beyond 67% molar, since at a higher AlCl3 content the melting point of the mixture climbs beyond 100° C.
Other reactions studied include the acylation of naphthalene and anthracene; the cracking of polyethylene; and the isomerization of fatty acids; all performed in acidic chloroaluminate melts.
The use of the Lewis acid FeCl3 to form acidic ionic liquids in the system [EMIMI]Cl-FeCl3 has also been described. Here too, an excess of Lewis acid is used, although only mixtures that have a molar FeCl3 content of less than 62% are liquid at temperatures below 100° C. The acylation of benzene with acyl chloride has been described, wherein the ketone that is formed is separated from the catalyst phase by means of extraction, when the molar FeCl3 content in the catalytically active mixture lies between 51 and 55 mol %.
In addition to the catalytically active ionic liquids that are formed by combining an excess of a Lewis acid with an organic chloride salt, a small number of other examples have been described in which Lewis acids such as scandium (III) triflate and other lanthanoid salts were mixed with a neutral ionic liquid containing [PF6]−, [BF4]−, [SbF6]−, or triflate ion in order to obtain a catalytically active system. However, in all such systems the Lewis acid is used at very low levels relative to the ionic liquid. Typically, mixtures have molar ratios of one part Lewis acid to 27 parts neutral ionic liquid. The resulting systems have been used to alkylate benzene with 1-hexene.
Mixtures of lanthanoid triflate salts and neutral ionic liquid containing [PF6]−, [BF4]−, [SbF6]−, or triflate ion have also been described in which the lanthanoid is used as a Lewis acid at a very low molar ratio relative to the ionic liquid. The molar ratio between the lanthanoid triflate and the ionic liquid is typically 1:200. These mixtures have been used to achieve a 3-component synthesis of α-aminophosphonates. An important limitation in the industrial usefulness of the concept is the known decomposition of labile complex anions (such as [PF6]−, [SbF6]−,)) in the presence of strong Lewis acids.
Fundamentally different, catalytically active, acidic Ionic liquids have been developed and used, for example, in the Friedel-Crafts alkylation of benzene with decene. Examples include an ionic liquids which are mixtures of [BMIM][HSO4] and the Brønsted acid sulfuric acid, substantially free of Lewis acidity; these mixtures were unable to achieve an acidity exceeding that of pure sulfuric acid.
Other acidic ionic liquids based on a similar concept include a mixture of tributylhexylammonium-bis(trifluoromethanesulfonyl)imide ([NBu3(C6H13)][(CF3SO2)2N]) and a Brønsted acid in acid-catalyzed cyclization reactions. Phosphoric acid and toluene sulfonic acid have also been used as Brønsted acids. However, there is a problem in that if even stronger Brønsted acids are added to a bis(trifluoromethanesulfonyl)amide melt, the free acid of the anion is formed, which sublimates easily at low temperatures.
In general, it can be seen from the previously disclosed uses of acidic Ionic liquids in various acid-catalyzed reactions that the use of acidic, liquid salts as catalysts is promising from an industrial point of view. The prior-art acidic ionic liquids possess variable acidity in certain ranges and interesting solubility characteristics that can be varied by the nature of the cation. These solubility characteristics allow new approaches to the industrial implementation of acid-catalyzed reactions, for example by using a multiple-phase reaction regime.